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The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with immune escape ability raises the urgent need for developing cross-neutralizing vaccines against the virus. NVSI-06-08 is a potential broad-spectrum recombinant COVID-19 vaccine that integrates the antigens from multiple SARS-CoV-2 strains into a single immunogen. Here, we evaluated the safety and immunogenicity of NVSI-06-08 as a heterologous booster dose in adults previously vaccinated with the inactivated vaccine BBIBP-CorV in a randomized, double-blind, controlled, phase 2 trial conducted in the United Arab Emirates (NCT05069129). Three groups of healthy adults over 18 years of age (600 participants per group) who had administered two doses of BBIBP-CorV 4-6-month, 7-9-month and >9-month earlier, respectively, were vaccinated with either a homologous booster of BBIBP-CorV or a heterologous booster of NVSI-06-08. The primary outcome was immunogenicity and safety of booster vaccinations. The exploratory outcome was cross-reactive immunogenicity against multiple SARS-CoV-2 variants of concerns (VOCs). The incidence of adverse reactions was low in both booster vaccinations, and the overall safety profile of heterologous boost was quite similar to that of homologous boost. Heterologous NVSI-06-08 booster was immunogenically superior to homologous booster of BBIBP-CorV. Both Neutralizing and IgG antibodies elicited by NVSI-06-08 booster were significantly higher than by the booster of BBIBP-CorV against not only SARS-CoV-2 prototype strain but also multiple VOCs. Especially, the neutralizing activity induced by NVSI-06-08 booster against the immune-evasive Beta variant was no less than that against the prototype strain, and a considerable level of neutralizing antibodies against Omicron (GMT: 367.67; 95%CI, 295.50-457.47) was induced by heterologous booster, which was substantially higher than that boosted by BBIBP-CorV (GMT: 45.03; 95%CI, 36.37-55.74). Our findings showed that NVSI-06-08 was safe and immunogenic as a booster dose following two doses of BBIBP-CorV, which was immunogenically superior to homologous boost with another dose of BBIBP-CorV. Our study also indicated that the design of hybrid antigen may provide an effective strategy for broad-spectrum vaccine developments.
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BackgroundThe increased coronavirus disease 2019 (COVID-19) breakthrough cases pose the need of booster vaccinations. In this study, we reported the safety and immunogenicity of a heterologous boost with a recombinant COVID-19 vaccine (CHO cells), named NVSI-06-07, as a third dose in participants who have previously received two doses of the inactivated vaccine (BBIBP-CorV) at pre-specified time intervals. Using homologous boost with BBIBP-CorV as control, the safety and immunogenicity of the heterologous boost with NVSI-06-07 against various SARS-CoV-2 strains, including Omicron, were characterized. MethodsThis study is a single-center, randomised, double-blinded, controlled phase 2 trial for heterologous boost of NVSI-06-07 in BBIBP-CorV recipients from the United Arab Emirates (UAE). Healthy adults (aged [≥]18 years) were enrolled and grouped by the specified prior vaccination interval of BBIBP-CorV, i.e., 1-3 months, 4-6 months or [≥]6 months, respectively, with 600 individuals per group. For each group, participants were randomly assigned at 1:1 ratio to receive either a heterologous boost of NVSI-06-07 or a homologous booster dose of BBIBP-CorV. The primary outcome was to comparatively assess the immunogenicity between heterologous and homologous boosts at 14 and 28 days post-boosting immunization, by evaluation of the geometric mean titers (GMTs) of IgG and neutralizing antibodies as well as the corresponding seroconversion rate ([≥]4-fold rise in antibody titers). The secondary outcomes were the safety profile of the boosting strategies within 30 days post vaccination. The exploratory outcome was the immune efficacy against Omicron and other variants of concern (VOCs) of SARS-CoV-2. This trial is registered with ClinicalTrials.gov, NCT05033847. FindingsA total of 1800 individuals who have received two doses of BBIBP-CorV were enrolled, of which 899 participants received a heterologous boost of NVSI-06-07 and 901 received a homologous boost for comparison. No vaccine-related serious adverse event (SAE) and no adverse events of special interest (AESI) were reported. 184 (20{middle dot}47%) participants in the heterologous boost groups and 177 (19{middle dot}64%) in the homologous boost groups reported at least one adverse reaction within 30 days. Most of the local and systemic adverse reactions reported were grades 1 (mild) or 2 (moderate), and there was no significant difference in the overall safety between heterologous and homologous boosts. Immunogenicity assays showed that the seroconversion rates in neutralizing antibodies against prototype SARS-CoV-2 elicited by heterologous boost were 89{middle dot}96% - 97{middle dot}52% on day 28 post-boosting vaccination, which was much higher than what was induced by homologous boost (36{middle dot}80% - 81{middle dot}75%). Similarly, in heterologous NVSI-06-07 booster groups, the neutralizing geometric mean titers (GMTs) against the prototype strain increased by 21{middle dot}01 - 63{middle dot}85 folds from baseline to 28 days post-boosting vaccination, whereas only 4{middle dot}20 - 16{middle dot}78 folds of increases were observed in homologous BBIBP-CorV booster group. For Omicron variant, the neutralizing antibody GMT elicited by the homologous boost of BBIBP-CorV was 37{middle dot}91 (95%CI, 30{middle dot}35-47{middle dot}35), however, a significantly higher level of neutralizing antibodies with GMT 292{middle dot}53 (95%CI, 222{middle dot}81-384{middle dot}07) was induced by the heterologous boost of NVSI-06-07, suggesting that it may serve as an effective boosting strategy combating the pandemic of Omicron. The similar results were obtained for other VOCs, including Alpha, Beta and Delta, in which the neutralizing response elicited by the heterologous boost was also significantly greater than that of the homologous boost. In the participants primed with BBIBP-CorV over 6 months, the largest increase in the neutralizing GMTs was obtained both in the heterologous and homologous boost groups, and thus the booster vaccination with over 6 months intervals was optimal. InterpretationOur findings indicated that the heterologous boost with NVSI-06-07 was safe, well-tolerated and immunogenic in adults primed with a full regimen of BBIBP-CorV. Compared to homologous boost with a third dose of BBIBP-CorV, incremental increases in immune responses were achieved by the heterologous boost with NVSI-06-07 against SARS-CoV-2 prototype strain, Omicron variant, and other VOCs. The heterologous BBIBP-CorV/NVSI-06-07 prime-boosting vaccination may be valuable in preventing the pandemic of Omicron. The optimal booster strategy was the heterologous boost with NVSI-06-07 over 6 months after a priming with two doses of BBIBP-CorV. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for clinical trials or prospective/cohort studies involving heterologous booster vaccination in non-immunocompromised population published up to Dec 25, 2021, using the term "(COVID) AND (vaccin*) AND (clinical trial OR cohort OR prospective) AND (heterologous) AND (booster OR prime-boost OR third dose)" with no language restrictions. Nine studies of heterologous prime-boost vaccinations with adenovirus-vector vaccines (ChAdOx1 nCov-19, Oxford-AstraZeneca, Ad26.COV2.S, Janssen) and mRNA vaccines (BNT162b2, Pfizer-BioNtech; mRNA1273, Moderna) were identified. The adenovirus-vector and mRNA heterologous prime-boost vaccination was found to be well tolerated and immunogenic. In individuals primed with adenovirus-vector vaccine, mRNA booster vaccination led to greater immune response than homologous boost. However, varied results were obtained on whether heterologous boost was immunogenically superior to the homologous mRNA prime-boost vaccination. Besides that, A preprint trial in population previously immunized with inactivated vaccines (CoronaVac, Sinovac Biotech) showed that the heterologous boost with adenovirus-vector vaccine (Convidecia, CanSino Biologicals) was safe and induced higher level of live-virus neutralizing antibodies than by the homogeneous boost. A pilot study reported that boosting with BNT162b2 in individuals primed with two doses of inactivated vaccines (BBIBP-CorV) was significantly more immunogenic than homologous vaccination with two-dose of BNT162b2. In addition, a preprint paper demonstrated that heterologous boost of ZF2001, a recombinant protein subunit vaccine, after CoronaVac or BBIBP-CorV vaccination potently improved the immunogenicity. But only a small size of samples was tested in this study and the live-virus neutralization was not detected. Till now, it is still lacking a formal clinical trial to evaluate the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated vaccine followed by a recombinant protein subunit-based vaccine. Added value of this studyTo our knowledge, this is the first reported result of a large-scale randomised, controlled clinical trial of heterologous prime-boost vaccination with an inactivated vaccine followed by a recombinant protein subunit vaccine. This trial demonstrated that the heterologous prime-booster vaccination with BBIBP-CorV/NVSI-06-07 is safe and immunogenic. Its immunoreactivity is similar to that of homologous vaccination with BBIBP-CorV. Compared to homologous boost, heterologous boost with NVSI-06-07 in BBIBP-CorV recipients elicited significantly higher immunogenicity not only against the SARS-CoV-2 prototype strain but also against Omicron and other variants of concern (VOCs). Implications of all the available evidenceBooster vaccination is considered an effective strategy to improve the protection efficacy of COVID-19 vaccines and control the epidemic waves of SARS-CoV-2. Data from our trial suggested that the booster vaccination of NVSI-06-07 in BBIBP-CorV recipients significantly improved the immune responses against various SARS-CoV-2 strains, including Omicron. Due to no Omicron-specific vaccine available currently, the BBIBP-CorV/NVSI-06-07 heterologous prime-boost might serve as an effective strategy combating Omicron variant. Besides that, BBIBP-CorV has been widely inoculated in population, and thus further boosting vaccination with NVSI-06-07 is valuable in preventing the COVID-19 pandemic. But further studies are needed to assess the long-term protection of BBIBP-CorV/NVSI-06-07 prime-booster vaccination.
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Objective@#To understand the situation of ticks carrying pathogens in border areas of Heilongjiang province.@*Methods@#From 2009 to 2018, tick specimens were collected in Yichun, Daxing′anling area and Jiamusi in Heilongjiang province. A total of 2 530 ticks were studied, including 800 Ixodes persulcatus and 1 730 Dermacentor silvarum. Tick-borne encephalitis virus (TBEV), severe fever with thrombocytopenia syndrome virus (SFTSV), omsk hemorrhagic fever virus (OHFV), langat virus (LGTV), powassan virus (POWV) were detected by real-time RT-PCR. Spotted fever group rickettsia (SFGR) and Borrelia burgdorferi sensulato (B.b.s.l) were detected by PCR in ticks collected from Jiamusi area.@*Results@#All tick speciments collected were negative for TBEV, SFTSV, OHFV, LGTV and POWV. Tick specimens from Jiamusi carried SFGR and B. b.s.l.with positive rates of 59.5% and 8.9%.@*Conclusions@#The ticks in border areas of Heilongjiang province carry spotted fever group rickettsia and Borrelia burgdorferi, and the carrying rate of spotted fever group rickettsia is high. The monitoring and control of ticks and tick-borne diseases should be strengthened.
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Objective@#To investigate the west nile virus (WNV) infection in Xinjiang, China.@*Methods@#Serum samples were collected from patients with fever and chicken in southern Xinjiang, 2012. The presence of WNV-specific immunoglobulin M (IgM) antibodies and neutralizing antibodies was examined through enzyme-linked immunosorbent assay (ELISA) and plaque reduction neutraization test (PRNT90).@*Results@#A total of 1 712 serum samples of outpatients and inpatients were collected in 8 counties in southern Xinjiang. As a result , 22 samples were positive for WNV IgM antibody and 48 samples were positive for WNV neutralization antibody, among which 21 WNV IgM antibody positive samples and 42 WNV neutralization antibody positive samples were from Jiashi county. Of 383 chicken serum samples collected in 4 counties in southern Xinjiang, only 28 samples were positive for WNV neutralizing antibody, interestingly, all positive chicken serum samples were collected from Jiashi county.@*Conclusions@#This study revealed that WNV infection occurred in human and poultry in southern Xinjiang, 2012, mainly in Jiashi county.
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Objective@#To analyze the epidemiological characteristics and distribution characteristics of tick-borne encephalitis in China in 2014, and to provide scientific basis for formulating specific prevention and control measures.@*Methods@#The epidemic data were obtained from the "infectious disease report information management system" , using Excel 2016, GIS and other software to summarize and analyze the cases of tick borne encephalitis (TBE) reported, using the number of cases, incidence, composition ratio and other indicators to analyze and describe the TBE epidemiological characteristics in China in 2014.@*Results@#In 2014, a total of 322 cases of TBE were reported in 9 provinces in China, with an annual incidence of 0.024/100, 000 and 1 death of patient. The provinces with high number of cases were Jilin province, Inner mongolia autonomous region and Heilongjiang province, and the number of cases in the other six provinces is no more than two. TBE was distributed in spring and summer, and it is concentrated in May to July. The age of the affected population was mostly concentrated in 40-49 years old, the male-female ratio was 1.6∶1 (198/124), and the patients were dominantly farmers, household and unemployed workers, and forestry workers, they accounted for 49.40% (159/322), 26.40% (85/322) and 18.60% (60/322) of the national TBE cases respectively. The three hospitals that reported the most TBE cases in 2014 were Inner mongolia forestry general hospital, Jiangyuan People′s hospital of Baishan city, Jilin province and Mudanjiang forestry central hospital of Heilongjiang province. The number of reported cases in these three hospitals accounted for 68.6% of the whole country. The laboratory diagnosis rate of Inner mongolia forestry general hospital was the highest (91.9%).@*Conclusions@#In 2014, the incidence of TBE in China has continued to rise compared with the previous two years. The geographical focus is mainly on the forest areas of Daxing′anling, Xiaoxing′anling and Changbai Mountain.
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Objective@#To analysis the genotype of Japanese encephalitis virus (JEV) in mosquitoes from Shandong province.@*Methods@#Mosquitoes were collected between August and September in Weishan county, Junan county, and Kenli county of Shandong province in 2016. Viruses were isolated by BHK-21 cell and identified by molecular method . Real-Time RT-PCR was conducted to detect the Japanese encephalitis virus carried by the mosquitoes.@*Results@#A total of 8418 mosquitoes divided into 81 pools including 3 species, Culex tritaeniorhynchus, Anopheles sinensis and Armigeres obturbans. Eight Japanese encephalitis viruses were isolated; 23 pools were positive by JEV specific real-time RT-PCR. Phylogenetic analysis on E sequence of JEV showed all JEV strains belonged to genotype Ⅰ JEV, and new strains that were homogenous with previous JEV strains isolated from Shandong.@*Conclusions@#Genotype Ⅰ JEV was the dominant genotype in Shandong province.
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Objective To investigate the distribution patterns of mosquitoes,midges and related arboviruses in Sichuan province.Methods Blood-sucking insects were collected from houses and pens,using the ultraviolet lights.Mosquito samples were classified according to morphologic characteristics and then stored at liquid nitrogen.All samples were incubated with BHK-21 and C6/36 cells for virus isolation and then detected for their viral genes.Sequences of the virus were identified and analyzed by molecular biological software,such as BioEdit 7.0.5.3,MEGA 6.0.Results In total,17 019 mosquitoes from 3 genera and 4 species and 12 700 midges were collected from the southeast regions of Sichuan province in 2016 and 2017.Among them,79.4％ (13 519/17 019) belonged to Culex tritaeniorhynchus with 11.1％ (1 897/17 019) as Armigeres subalbatus,5.5％ (930/17 019) were Anopheles sinensis and 4.0％ (673/17 019) were Anopheles sinensis 3 virus strains that isolated from Culex tritaeniorhynchus were identified as type Ⅰ Japanese encephalitis virus.Seven pools of mosquitoes isolated from Hejiang county were identified Japanese encephalitis virus gene positive through PCR amplification.With 4 pool midges were detected positive for Akabane virus through PCR gene amplification while midges samples didn't have virus isolates.Conclusions Culex tritaeniorhynchus appeared the predominant species in the southeast regions of Sichuan.Japanese encephalitis virus transmitted by mosquitoes and Akabane virus by midges were prevalent in southeast Sichuan province.
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Objective To investigate the distribution patterns of mosquitoes,midges and related arboviruses in Sichuan province.Methods Blood-sucking insects were collected from houses and pens,using the ultraviolet lights.Mosquito samples were classified according to morphologic characteristics and then stored at liquid nitrogen.All samples were incubated with BHK-21 and C6/36 cells for virus isolation and then detected for their viral genes.Sequences of the virus were identified and analyzed by molecular biological software,such as BioEdit 7.0.5.3,MEGA 6.0.Results In total,17 019 mosquitoes from 3 genera and 4 species and 12 700 midges were collected from the southeast regions of Sichuan province in 2016 and 2017.Among them,79.4％ (13 519/17 019) belonged to Culex tritaeniorhynchus with 11.1％ (1 897/17 019) as Armigeres subalbatus,5.5％ (930/17 019) were Anopheles sinensis and 4.0％ (673/17 019) were Anopheles sinensis 3 virus strains that isolated from Culex tritaeniorhynchus were identified as type Ⅰ Japanese encephalitis virus.Seven pools of mosquitoes isolated from Hejiang county were identified Japanese encephalitis virus gene positive through PCR amplification.With 4 pool midges were detected positive for Akabane virus through PCR gene amplification while midges samples didn't have virus isolates.Conclusions Culex tritaeniorhynchus appeared the predominant species in the southeast regions of Sichuan.Japanese encephalitis virus transmitted by mosquitoes and Akabane virus by midges were prevalent in southeast Sichuan province.
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Objective@#To investigate the distribution patterns of arboviruses in Yunnan province near the China-Laos-Myanmar border, China, and to provide evidence for prevention and control of arboviruses diseases.@*Methods@#Mosquito samples were collected in Daluo county of Xishuangbanna Dai Autonomous Prefecture and Zhengdong county of Pu’er city in Yunnan province, 2012. Viruses were isolated from the samples by tissue culture, positive isolates were identified by RT-PCR with arbovirus species-specific primers, for further sequencing and phylogenetic analysis.@*Results@#A total of 17 species of mosquitoes from 6 genera were collected. A total of 24 strains of viruses were isolated from the mosquito pools and identified as Tembusu virus (TMUV) (2 strains), Japanese encephalitis virus (JEV) (3 strains), Getah virus (GETV) (2 strains), Banna virus (BAV) (4 strains), Densovirus (DNV) (9 strains) and Nam Dinh virus (NDiV) (3 strains).@*Conclusions@#The China-Laos-Myanmar border of Yunnan province is rich in species of mosquitoes and arboviruses.
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In order to investigate the molecular evolution and spatio-temporal migration of Getah viruses (GETV) isolated around the world,the nucleotide and deduced amino acid sequence of GETVs were analyzed and phylogenetic trees were constructed by using informatics software including ClustalX1.83,MegaAlign,GeneDOC and Mega6.0.The Bayesian Stochastic Search Variable Selection (BSSVS) program in the BEAST v 1.8.1 software package was used to analyze the spatial dynamics of the Getah virus.Results showed that the full-length of Getah virus E2 gene consists of 1 266 nueleotides,encoding 422 amino acids.And the homology of nucleotide and amino acid were 94.5％ 100％ and 96.4％ 100％ respectively.The molecular evolution analysis revealed that there were no species and geographical distribution difference existing among GETV host animals (e.g.horses and pigs) and vectors (e.g.mosquitoes).Bioinformatics analysis showed that GETV originated in Malaysia,then it was spread to Japan,China,South Korea,Mongolia,Russia,etc.GETV E2 gene was relatively stable since GETV was first isolated in 1955.The differences of species and geographical distribution did not exist among GETV host animals and vectors,and the virus has spread from tropical regions to Eurasian continent.Thus,strengthening the detection and monitoring of GETV and its infections in humans and livestock is critical.
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The quality control process throughout the Ebola virus nucleic acid detection in Sierra Leone-China Friendship Biological Safety Laboratory (SLE-CHN Biosafety Lab) was described in detail, in order to comprehensively display the scientific, rigorous, accurate and efficient practice in detection of Ebola virus of first batch detection team in SLE-CHN Biosafety Lab. Firstly, the key points of laboratory quality control system was described, including the managements and organizing, quality control documents and information management, instrument, reagents and supplies, assessment, facilities design and space allocation, laboratory maintenance and biosecurity. Secondly, the application of quality control methods in the whole process of the Ebola virus detection, including before the test, during the test and after the test, was analyzed. The excellent and professional laboratory staffs, the implementation of humanized management are the cornerstone of the success; High-level biological safety protection is the premise for effective quality control and completion of Ebola virus detection tasks. And professional logistics is prerequisite for launching the laboratory diagnosis of Ebola virus. The establishment and running of SLE-CHN Biosafety Lab has landmark significance for the friendship between Sierra Leone and China, and the lab becomes the most important base for Ebola virus laboratory testing in Sierra Leone.
